Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
Inflammatory Bowel Diseases (Impact Factor: 4.46). 01/2007; 13(1):42-50. DOI: 10.1002/ibd.20006
Source: PubMed


In children with inflammatory bowel disease (IBD) it is not known whether reductions in bone mineral density (BMD) are a consequence of bone turnover alterations and if BMD improves with treatment.
In a cohort of children with IBD, we prospectively measured indicators of bone remodeling, body mass index (BMI), disease activity, intact parathyroid hormone, serum IL-6, and insulin-like growth factor-I at diagnosis and then every 6 months for 2 years. BMD was determined annually using dual x-ray absorptiometry (DXA). BMD Z-scores were calculated using height/age. Baseline measurements and calcium intake were compared with a group of age- and sex-matched healthy children.
We observed that at diagnosis total body BMD Z-score (mean +/- SD) was -0.78 +/- 1.02 for Crohn's disease (CD, n = 58), -0.46 +/- 1.14 for ulcerative colitis (UC, n = 18), and -0.17 +/- 0.95 for control (CL, n = 49) (P < 0.01, CD versus CL). In CD, a BMD Z-score <-1.0 was associated with lower BMI and higher serum IL-6. Patients with CD and UC had low bone turnover. Activation of bone formation paralleled clinical improvement, but BMC gain was less than expected over the 2-year study period, especially in CD. Prednisone use did not correlate with low BMD.
Decreased bone turnover occurs in children newly diagnosed with IBD. Although indicators of osteoblast activity increase with clinical improvement, bone mineral accrual does not accelerate. Children with low BMI may be considered for BMD screening, since they are at risk for low bone mass.

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    • "Prior studies have demonstrated that IBD is both associated with bone loss [43-45], and increased fracture risk in adults [46]. Thus, the finding that a history of malabsorption or IBD was associated with decreased risk of low BMD in the univariate and multivariate analyses was unexpected. "
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    ABSTRACT: Background To identify factors that predict low bone mineral density (BMD) in pediatric patients referred for dual-energy x-ray absorptiometry assessments. Methods This is a retrospective cohort study of 304 children and adolescents referred for dual-energy x-ray absorptiometry assessments at a tertiary care center. Outcomes included risk factors which predicted a significant low bone density for age, defined as BMD Z-score ≤ -2.0 SD. A univariate analysis involved Chi-square, Fisher’s Exact test, and analysis of variance, and multivariate logistic regression models were constructed to determine predictors of low bone mineral density. Results In the multivariate logistic regression model, predictors of low bone mineral density included low body mass index Z-score (odds ratio 0.52, 95% confidence interval 0.39 – 0.69), low height Z-score (OR 0.71, 95% CI 0.57 – 0.88), vitamin D insufficiency (OR 3.97, 95% CI 2.08 – 7.59), and history of bone marrow transplant (OR 5.78, 95% CI 1.00 – 33.45). Conclusions Underlying health problems and associated treatments can impair bone mineral accrual. We identified risk factors most predictive of low bone mineral density in subjects referred for bone density measurement. Recognition of these factors may allow for earlier assessment to maximize bone mass in at-risk children.
    Full-text · Article · Feb 2013 · International Journal of Pediatric Endocrinology
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    • "Children with inflammatory bowel disease demonstrate decreased bone mineral density [1]. Risk factors include the use of steroids [2], defective nutritional status [3] and the inflammatory process itself [4]. "
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    ABSTRACT: Diminished bone mineral density (BMD) is of significant concern in pediatric inflammatory bowel disease (IBD). Exact etiology is debatable. The recognition of fibroblast growth factor 23 (FGF23), a phosphaturic hormone related to tumor necrosis factor alpha (TNF-α) makes it plausible to hypothesize its possible relation to this pathology. In this follow up case control study, BMD as well as serum levels of FGF23, calcium, phosphorus, alkaline phosphatase, creatinine, parathyroid hormone, 25 hydroxy vitamin D3 and 1, 25 dihydroxy vitamin D3 were measured in 47 children with IBD during flare and reassessed in the next remission. Low BMD was frequent during IBD flare (87.2%) with significant improvement after remission (44.7%). During disease flare, only 21.3% of patients had vitamin D deficiency, which was severe in 12.8%. During remission, all patients had normal vitamin D except for two patients with Crohn's disease (CD) who remained vitamin D deficient. Mean value of serum FGF23 was significantly higher among patients with IBD during flare compared to controls. It showed significant improvement during remission but not to the control values. 1, 25 dihydroxy vitamin D3, FGF23, serum calcium and urinary phosphorus were significant determinants of BMD in IBD patients. We can conclude that diminished BMD in childhood IBD is a common multifactorial problem. Elevated FGF23 would be a novel addition to the list of factors affecting bone mineral density in this context. Further molecular studies are warranted to display the exact interplay of these factors.
    Full-text · Article · May 2012 · BMC Gastroenterology
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    • "The predominant bone remodelling abnormality in inflammatory bowel disease appears to be a reduction in bone formation with inappropriately maintained bone resorption (Sylvester et al. 2007). In other states characterised by poor nutritional availability such as anorexia nervosa a similar uncoupling of bone resorption from formation with suppressed formation is seen (Soyka et al. 1999). "
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    ABSTRACT: Chronic inflammatory diseases of almost any cause are associated with bone loss. Bone loss is due to direct effects of inflammation, poor nutrition, reduced lean body mass, immobility and the effects of treatments, especially glucocorticoids. These mechanisms are complex and interrelated but are ultimately mediated through effects on the bone remodelling cycle. Inflammatory disease can increase bone resorption, decrease bone formation but most commonly impacts on both of these processes resulting in an uncoupling of bone formation from resorption in favour of excess resorption. This review will illustrate these interactions between inflammation and bone metabolism and discuss how these are, and might be, manipulated as therapies for inflammation related bone loss.
    Preview · Article · Jul 2009 · Journal of Endocrinology
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